Chemistry, Manufacturing, and Controls is the section of the IND concerned with how your product is made and qualified. Whether a small molecule, antibody, cell, oligo, viral, or gene therapy, or something completely different, FDA requires strict, consistent, and well-controlled manufacturing processes, as anything less unnecessarily increases risk to patients.
The basics of a CMC package include (but are not limited to!) clear answers to the following questions:
- What is the drug (IUPAC name, chemical structure, sequence, cell type, etc., as applicable)?
- How is it made?
- What should it look like?
- What are the byproducts?
- How is it purified?
- How pure is it?
- What else is used in formulation?
- How is it sterilized?
- How is it packaged?
- What is the variance of the process steps, and what are the implications?
- What are the Quality Assurance processes? Quality Control and release criteria?
Your drug’s target product profile (TPP) should contain brief answers to most of the content in the “Chemistry” section of the CMC. “Manufacturing and Controls” details the process engineering applied to the production of your drug.
CMC is one of the later preclinical activities. Only after you’ve settled on your candidate drug and gone some way into formulation does CMC begin. That said, if you’re working with a non-standard modality, or know that the manufacturing processes will be complex in any particular way (e.g. sterilization of dispersions can be challenging – many CMOs are incapable), some consideration of the CMC challenges earlier in the development process is merited, if only to fully understand the magnitude of the challenge.
An excellent drug poorly made has the potential to be deadly. CMC is all about ensuring consistency in safety.
Contents and requirements for a successful CMC section of an IND.